The present invention relates to a series of new dihydropyridine derivatives, and provides a process for preparing them as well as means for their pharmaceutical use.
Circulatory and coronary disorders are amongst the major causes of death in the industrialized world and, even where they do not result in death, disablement or a severe curtailment of lifestyle may result. Notwithstanding this, the full etiology of such disorders has not been resolved, even though certain factors, notably genetic and dietary factors, have been implicated. There is, therefore, a substantial need for medicines to treat this major problem. In attempting to treat circulatory and coronary disorders, attention has been focused on a variety of different pharmacodynamic activities, and the drugs used in such treatment have a variety of different structures, depending upon the particular pharmacodynamic activity which it it is desired to influence.
Of the many classes of drug proposed for use in such treatment, some compounds have a 4-(substituted phenyl)-1,4-dihydropyridine basic structure and included within such general classes of drug are Nifedipine (which is included amongst the compounds disclosed in British Patent Specification No. 1,173,862) and Nicardipine (which is included amongst the compounds disclosed in British Patent Specification No. 1,455,502). All of these compounds have in common a 4-(nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid ester structure.
However, it is believed that the closest prior art to the compounds of the present invention is disclosed in Arzneim.--Forsh., 31, 1173 (1981) and in European Patent Publication No. 125 803. Both of these disclose compounds which are said to have cardiovascular activity, in much the same way as do the compounds of the present invention. However, the compounds of the former prior art differ from those of the present invention in the nature of the ester grouping at the 1,4-dihydropyridine system. The latter prior art, although disclosing compounds some of which have an ester grouping resembling that of the present invention, differ in the overall structure of the compounds and notably in the nature of the groups at the 2- and 6-positions of the dihydropyridine ring.
Other related compounds are disclosed in U.S. patent application Ser. No. 873,946, filed the 13th day of June, 1986, which has been replaced by continuation application Ser. No. 146,713 filed Jan. 21, 1988, but these differ from the compounds of the present invention in that the prior compounds contain a nitrooxy group in their molecular structure, which is not possessed by the compounds of the present invention.